A major area of interest concerning the problem of regeneration is identification of specific neuronal and glial response to injury in the vertebrate central (CNS) and peripheral (PNS) nervous systems. In the developing and mature nervous system, neurons and glia establish relationships which constitute morphological and physiological units. Under pathological conditions not only are the spectra of individual cell changes important, but the manner in which these cells interact is also of considerable significance in determining the ultimate success or failure of the regenerative process. For example, in mammals neuroglial scar formation is considered to be a major impediment to regeneration. On the other hand, ultrastructural studies of nonmammalian vertebrates suggest that neuroglia form a facilitative, rather than prohibitive, framework for axonal outgrowth. The objectives of the following series of proposed investigations are: (1) to examine and compare by autoradiographic, cytochemical and conventional ultrastructural techniques the cytology, cellular organization, and population kinetics characteristics of neurons and glia subsequent to optic nerve and/or spinal cord transection in amphibians, fish and mammals; and (2) to study by application of the freeze-fracture method, alterations in membranes related to neuron-glial and glial-glial surface contacts during degeneration, regeneration, and remyelination in the CNS and PNS. Comparative analysis of neuronal and glial dynamics will be focused on species exhibiting differential regenerative abilities superimposed upon neural tissue comprised of similar cellular elements. Observations made should provide a more complete definition of the roles played by glia in developing a milieu either conducive or restrictive to regeneration and will contribute to an identification of cellular mechanisms which are essential for successful structural and functional recovery.